Lanzhou University Second Hospital

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Having a hypoxic microenvironment is a common and salient feature of most solid tumors. Hypoxia has a profound effect on the biological behavior and malignant phenotype of cancer cells, mediates the effects of cancer chemotherapy, radiotherapy, and immunotherapy through complex mechanisms, and is closely associated with poor prognosis in various cancer patients. Accumulating studies have demonstrated that through normalization of the tumor vasculature, nanoparticle carriers and biocarriers can effectively increase the oxygen concentration in the tumor microenvironment, improve drug delivery and the efficacy of radiotherapy. They also increase infiltration of innate and adaptive anti-tumor immune cells to enhance the efficacy of immunotherapy. Furthermore, drugs targeting key genes associated with hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, and drugs targeting hypoxia-inducible factors and downstream targets, can be used for visualization and quantitative analysis of tumor hypoxia and antitumor activity. However, the relationship between hypoxia and cancer is an area of research that requires further exploration. Here, we investigated the potential factors in the development of hypoxia in cancer, changes in signaling pathways that occur in cancer cells to adapt to hypoxic environments, the mechanisms of hypoxia-induced cancer immune tolerance, chemotherapeutic tolerance, and enhanced radiation tolerance, as well as the insights and applications of hypoxia in cancer therapy.

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 μg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).

OBJECTIVES: To investigate the prevalence and associated factors of kidney stones among adults in China. SUBJECTS AND METHODS: A nationwide cross-sectional survey was conducted among individuals aged ≥18 years across China, from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, completed pre-designed and standardised questionnaires, and provided blood and urine samples for analysis. Kidney stones were defined as particles of ≥4 mm. Prevalence was defined as the proportion of participants with kidney stones and binary logistic regression was used to estimate the associated factors. RESULTS: A total of 12 570 individuals (45.2% men) with a mean (sd, range) age of 48.8 (15.3, 18-96) years were selected and invited to participate in the study. In all, 9310 (40.7% men) participants completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% [95% confidence interval (CI) 5.9, 6.9], and the age- and sex-adjusted prevalence was 5.8% (95% CI 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male gender, rural residency, age, family history of urinary stones, concurrent diabetes mellitus and hyperuricaemia, increased consumption of meat, and excessive sweating were all statistically significantly associated with a greater risk of kidney stones. By contrast, consumption of more tea, legumes, and fermented vinegar was statistically significantly associated with a lesser risk of kidney stone formation. CONCLUSION: Kidney stones are common among Chinese adults, with about one in 17 adults affected currently. Some Chinese dietary habits may lower the risk of kidney stone formation.

OBJECTIVE: We aimed to evaluate the performance of the newly developed deep learning Radiomics of elastography (DLRE) for assessing liver fibrosis stages. DLRE adopts the radiomic strategy for quantitative analysis of the heterogeneity in two-dimensional shear wave elastography (2D-SWE) images. DESIGN: A prospective multicentre study was conducted to assess its accuracy in patients with chronic hepatitis B, in comparison with 2D-SWE, aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors, by using liver biopsy as the reference standard. Its accuracy and robustness were also investigated by applying different number of acquisitions and different training cohorts, respectively. Data of 654 potentially eligible patients were prospectively enrolled from 12 hospitals, and finally 398 patients with 1990 images were included. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the optimal area under the ROC curve (AUC) for cirrhosis (F4), advanced fibrosis (≥F3) and significance fibrosis (≥F2). RESULTS: AUCs of DLRE were 0.97 for F4 (95% CI 0.94 to 0.99), 0.98 for ≥F3 (95% CI 0.96 to 1.00) and 0.85 (95% CI 0.81 to 0.89) for ≥F2, which were significantly better than other methods except 2D-SWE in ≥F2. Its diagnostic accuracy improved as more images (especially ≥3 images) were acquired from each individual. No significant variation of the performance was found if different training cohorts were applied. CONCLUSION: DLRE shows the best overall performance in predicting liver fibrosis stages compared with 2D-SWE and biomarkers. It is valuable and practical for the non-invasive accurate diagnosis of liver fibrosis stages in HBV-infected patients. TRIAL REGISTRATION NUMBER: NCT02313649; Post-results.

Tumor immune microenvironment (TIME) include tumor cells, immune cells, cytokines, etc. The interactions between these components, which are divided into anti-tumor and pro-tumor, determine the trend of anti-tumor immunity. Although the immune system can eliminate tumor through the cancer-immune cycle, tumors appear to eventually evade from immune surveillance by shaping an immunosuppressive microenvironment. Immunotherapy reshapes the TIME and restores the tumor killing ability of anti-tumor immune cells. Herein, we review the function of immune cells within the TIME and discuss the contribution of current mainstream immunotherapeutic approaches to remolding the TIME. Changes in the immune microenvironment in different forms under the intervention of immunotherapy can shed light on better combination treatment strategies.

Hereditary hearing impairment is one of the major and common birth defects in Chinese population. Non-syndromic sensorineural hearing loss (NSHL) is the most common types of hereditary hearing impairment. Genotypically and phenotypically NSHL is extremely heterogenous and follow either autosomal dominant, or autosomal recessive or X-linked mode of inheritance. Presently, 127 genes have been identified to be associated with both syndromic and non-syndromic sensorineural hearing loss. Here, we studied a Chinese family with moderate and profound hearing impairment. The proband is a 30-year old Chinese man. The proband was born with normal hearing and at the age of 5-years,the proband was first noticed with hearing impairment. Gradually and progressively the proband was presented with loss of hearing in his both right and left ears at the age of 30 years. The clinical symptoms, age of onset or progression to loss of hearing was similar in both the proband and his younger brother. The proband’s parents are phenotypically normal and non-consanguineous. Clinical diagnosis of the proband and his younger brother has been done by classical pure tone audiogram (PTA). Computed Tomography (CT) found no abnormality in bilateral external ear, middle ear and inner ear. Targeted next generation sequencing was performed with a panel of 127 genes reported to be associated with hereditary hearing impairment. A novel homozygous single nucleotide deletion (c.427delT) in exon 4 of ILDR1 gene has been identified in proband and in his younger brother. Sanger sequencing confirmed that proband’s father and mother are carrying this mutation in a heterozygous manner. This mutation has not been identified in 100 normal healthy control individuals. This mutation (c.427delT) causes frameshift (p.Tyr143Ilefs*19) which leads to the formation of a truncated ILDR1 protein of 162 amino acids instead of the wild type ILDR1 protein of 546 amino acids. ILDR1 associated hereditary hearing impairment is very rare and this is the first report of identifying a loss-of-function mutation in ILDR1 gene associated with hereditary hearing impairment in Chinese population. Our present study also emphasized the significance of rapid, accurate and cost-effective screening for the patient with hereditary hearing impairment by targeted next generation sequencing.

Aldehyde dehydrogenase isoform 1 (ALDH1) has been proved useful for the identification of cancer stem cells. However, our knowledge of the expression and activity of ALDH1 in common epithelial cancers and their corresponding normal tissues is still largely absent. Therefore, we characterized ALDH1 expression in 24 types of normal tissues and a large collection of epithelial tumor specimens (six cancer types, n = 792) by immunohistochemical staining. Using the ALDEFUOR assay, ALDH1 activity was also examined in 16 primary tumor specimens and 43 established epithelial cancer cell lines. In addition, an ovarian cancer transgenic mouse model and 7 murine ovarian cancer cell lines were analyzed. We found that the expression levels and patterns of ALDH1 in epithelial cancers are remarkably distinct, and they correlate with their corresponding normal tissues. ALDH1 protein expression levels are positively correlated with ALDH1 enzymatic activity measured by ALDEFLUOR assay. Long-term in vitro culture doesn't significantly affect ALDH1 activity in epithelial tumor cells. Consistent with research on other cancers, we found that high ALDH1 expression is significantly associated with poor clinical outcomes in serous ovarian cancer patients (n = 439, p = 0.0036). Finally, ALDH(br) tumor cells exhibit cancer stem cell properties and are resistant to chemotherapy. As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.

Chitosan-alginate (CS/ALG) nanoparticles were prepared by ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation, nifedipine was chosen as a model drug. Morphology and structure characterization of nanoparticles were investigated by transmission electron microscope (TEM) and Fourier transform infrared spectra (FTIR), respectively. The diameter of the nanoparticles was about 20-50 nm, suitable for uptake within the gastrointestinal tract due to their nanosize range and mucoadhesive properties. A reversed-phase high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of nifedipine in nanoparticulate dosage forms. In addition, the delivery behavior of nifedipine from nanoparticles was studied. Nifedipine released from chitosan-alginate nanoparticles was 26.52% at pH1.5, 69.69% at pH6.8 and 56.50% at pH7.4 within 24hour. This suggests that the release of nifedipine from nanoparticles was pH-responsive. Quick release occurred in simulated intestinal fluid (SIF, pH6.8) and phosphate buffer solution (pH7.4), while the release was slow in simulated gastric fluid (SGF, pH1.5). The release profile was characterized by an initial burst effect in three media, followed by a continuous and controlled release phase, the drug release mechanism from polymer was due to Fickian diffusion.

Hypertension is a major cause of cardiovascular disease and deaths worldwide especially in low- and middle-income countries. Despite the availability of safe, well-tolerated, and cost-effective blood pressure (BP)-lowering therapies, <14% of adults with hypertension have BP controlled to a systolic/diastolic BP <140/90 mm Hg. We report new hypertension treatment guidelines, developed in accordance with the World Health Organization Handbook for Guideline Development. Overviews of reviews of the evidence were conducted and summary tables were developed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. In these guidelines, the World Health Organization provides the most current and relevant evidence-based guidance for the pharmacological treatment of nonpregnant adults with hypertension. The recommendations pertain to adults with an accurate diagnosis of hypertension who have already received lifestyle modification counseling. The guidelines recommend BP threshold to initiate pharmacological therapy, BP treatment targets, intervals for follow-up visits, and best use of health care workers in the management of hypertension. The guidelines provide guidance for choice of monotherapy or dual therapy, treatment with single pill combination medications, and use of treatment algorithms for hypertension management. Strength of the recommendations was guided by the quality of the underlying evidence; the tradeoffs between desirable and undesirable effects; patient's values, resource considerations and cost-effectiveness; health equity; acceptability, and feasibility consideration of different treatment options. The goal of the guideline is to facilitate standard approaches to pharmacological treatment and management of hypertension which, if widely implemented, will increase the hypertension control rate world-wide.

The gut microbiota and its homeostasis play a crucial role in human health. However, for some diseases related to the gut microbiota, current traditional medicines can only relieve symptoms, and it is difficult to solve the root causes or even cause side effects like disturbances in the gut microbiota. Increasing clinical studies and evidences have demonstrated that probiotics, prebiotics, and postbiotics can prevent and treat various diseases, but currently they can only be used as dietary supplements rather than medicines, which restricts the application of probiotics in the field of medicine. Here, this review analyzes the importance of gut microbiota in human health and the current problems of traditional medicines, and systematically summarizes the effectiveness and mechanisms of probiotics, prebiotics, and postbiotics in maintaining health and treating diseases based on animal models and clinical trials. And based on current research outcomes and development trends in this field, the challenges and prospects of their clinical application in maintaining health, alleviating and treating diseases are analyzed. It is hoped to promote the application of probiotics, prebiotics, and postbiotics in disease treatment and open up new frontiers in probiotic research.

(1) Background: To review the associated factors of sarcopenia in community-dwelling older adults. (2) Methods: PubMed, Embase, Web of Science, and four Chinese electronic databases were searched for observational studies that reported the associated factors of sarcopenia from inception to August 2021. Two researchers independently selected the literature, evaluated their quality, and extracted relevant data. The pooled odds ratio (OR) and its 95% confidence interval (CI) were calculated for each associated factors of sarcopenia using random-effects/fixed-effects models. Publication bias was assessed using funnel plot and the Eggers test. We performed statistical analysis using Stata 15.0 software. (3) Results: A total of 68 studies comprising 98,502 cases were included. Sociodemographic associated factors of sarcopenia among community-dwelling older adults included age (OR = 1.12, 95% CI: 1.10-1.13), marital status (singled, divorced, or widowed) (OR = 1.57, 95% CI: 1.08-2.28), disability for activities of daily living (ADL) (OR = 1.49, 95% CI: 1.15-1.92), and underweight (OR = 3.78, 95% CI: 2.55-5.60). Behavioral associated factors included smoking (OR = 1.20, 95% CI: 1.10-1.21), physical inactivity (OR = 1.73, 95% CI: 1.48-2.01), malnutrition/malnutrition risk (OR = 2.99, 95% CI: 2.40-3.72), long (OR = 2.30, 95% CI: 1.37-3.86) and short (OR = 3.32, 95% CI: 1.86-5.93) sleeping time, and living alone (OR = 1.55, 95% CI: 1.00-2.40). Disease-related associated factors included diabetes (OR = 1.40, 95% CI: 1.18-1.66), cognitive impairment (OR = 1.62, 95% CI: 1.05-2.51), heart diseases (OR = 1.14, 95% CI: 1.00-1.30), respiratory diseases (OR = 1.22, 95% CI: 1.09-1.36), osteopenia/osteoporosis (OR = 2.73, 95% CI: 1.63-4.57), osteoarthritis (OR = 1.33, 95% CI: 1.23-1.44), depression (OR = 1.46, 95% CI: 1.17-1.83), falls (OR = 1.28, 95% CI: 1.14-1.44), anorexia (OR = 1.50, 95% CI: 1.14-1.96), and anemia (OR = 1.39, 95% CI: 1.06-1.82). However, it remained unknown whether gender (female: OR = 1.10, 95% CI: 0.80-1.51; male: OR = 1.50, 95% CI: 0.96-2.34), overweight/obesity (OR = 0.27, 95% CI: 0.17-0.44), drinking (OR = 0.92, 95% CI: 0.84-1.01), hypertension (OR = 0.98, 95% CI: 0.84-1.14), hyperlipidemia (OR = 1.14, 95% CI: 0.89-1.47), stroke (OR = 1.70, 95% CI: 0.69-4.17), cancer (OR = 0.88, 95% CI: 0.85-0.92), pain (OR = 1.08, 95% CI: 0.98-1.20), liver disease (OR = 0.88, 95% CI: 0.85-0.91), and kidney disease (OR = 2.52, 95% CI: 0.19-33.30) were associated with sarcopenia. (4) Conclusions: There are many sociodemographic, behavioral, and disease-related associated factors of sarcopenia in community-dwelling older adults. Our view provides evidence for the early identification of high-risk individuals and the development of relevant interventions to prevent sarcopenia in community-dwelling older adults.

Long non-coding RNAs (lncRNAs) are RNA molecules with a transcript length of more than 200 nt and lack a protein-coding ability. They regulate gene expression by interacting with protein, RNA, and DNA. Their function is closely related to their subcellular localization. In the nucleus, lncRNAs regulate gene expression at the epigenetic and transcriptional levels, and in the cytoplasm, they regulate gene expression at the post-transcriptional and translational levels. Abnormalities in lncRNAs have been confirmed to exhibit tumor suppressor or carcinogenic effects and play an important role in the development of tumors. In particular, the lung cancer-related transcript 1 (LUCAT1) located in the antisense strand of the q14.3 region of chromosome 5 was first discovered in smoking-related lung cancer. Increasing evidence have showed that LUCAT1 is involved in breast cancer, ovarian cancer, thyroid cancer, renal cell carcinoma. It is highly expressed in liver cancer and other malignant tumors and has been confirmed to be induce various malignant tumors. It regulates tumor proliferation, invasion, and migration via various mechanisms and is related to the clinicopathological characteristics of tumor patients. Thus, LUCAT1 is a potential prognostic biological marker and therapeutic target for cancer. This article reviews its expression, function, and molecular mechanism in various malignant tumors.

SUMOylation is a reversible post-translational modification which has emerged as a crucial molecular regulatory mechanism, involved in the regulation of DNA damage repair, immune responses, carcinogenesis, cell cycle progression and apoptosis. Four SUMO isoforms have been identified, which are SUMO1, SUMO2/3 and SUMO4. The small ubiquitin-like modifier (SUMO) pathway is conserved in all eukaryotes and plays pivotal roles in the regulation of gene expression, cellular signaling and the maintenance of genomic integrity. The SUMO catalytic cycle includes maturation, activation, conjugation, ligation and de-modification. The dysregulation of the SUMO system is associated with a number of diseases, particularly cancer. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis and apoptosis. SUMO can be used as a potential therapeutic target for cancer. In this review, we briefly outline the basic concepts of the SUMO system and summarize the involvement of SUMO proteins in cancer cells in order to better understand the role of SUMO in human disease.

One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors. Despite recent advances in diagnostic practices and surgical interventions, many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy. As a result, the prognosis for many patients afflicted with these aggressive cancers remains bleak. The insulin-like growth factor (IGF) signaling axis has been shown to play critical role in the development and progression of various tumors. Many basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various malignancies. There also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care therapy. By better understanding both the IGF-dependent and -independent mechanisms by which pathway members can influence drug sensitivity, we can eventually aim to use modulators of IGF signaling to augment the effects of current therapy. This review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug resistance. We offer a brief overview of IGF signaling and its general role in neoplasia, and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to therapy. Ultimately, our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance.

OBJECTS: Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of the spinal cord, which significantly impacts the quality of life in affected patients. The phosphoinositide 3kinase/serine-threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for the inhibition of secondary TSCI. This review summarizes updates concerning the role of the PI3K/AKT pathway in TSCI. MATERIALS AND METHODS: By searching articles related to the TSCI field and the PI3K/AKT signaling pathway, we summarized the mechanisms of secondary TSCI and the PI3K/AKT signaling pathway; we also discuss current and potential future treatment methods for TSCI based on the PI3K/AKT signaling pathway. RESULTS: Early apoptosis and autophagy after TSCI protect the body against injury; a prolonged inflammatory response leads to the accumulation of pro-inflammatory factors and excessive apoptosis, as well as excessive autophagy in the surrounding normal nerve cells, thus aggravating TSCI in the subacute stage of secondary injury. Initial glial scar formation in the subacute phase is a protective mechanism for TSCI, which limits the spread of damage and inflammation. However, mature scar tissue in the chronic phase hinders axon regeneration and prevents the recovery of nerve function. Activation of PI3K/AKT signaling pathway can inhibit the inflammatory response and apoptosis in the subacute phase after secondary TSCI; inhibiting this pathway in the chronic phase can reduce the formation of glial scar. CONCLUSION: The PI3K/AKT signaling pathway has an important role in the recovery of spinal cord function after secondary injury. Inducing the activation of PI3K/AKT signaling pathway in the subacute phase of secondary injury and inhibiting this pathway in the chronic phase may be one of the potential strategies for the treatment of TSCI.

BACKGROUND: The outbreak of novel coronavirus pneumonia (COVID-19) has brought enormous physical and psychological pressure on Chinese medical staff. It is extremely important to understand the prevalence and influencing factors of anxiety and depression symptoms in first-line anti-epidemic medical staff and their coping styles for these negative emotions. METHODS: A cross-sectional survey was conducted in Gansu (China), with a questionnaire packet which consisted of the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and the simplified coping style questionnaire (SCSQ). A total of 79 doctors and 86 nurses participated in the survey. Correlation analysis was performed to explore the relationship between SAS, SDS, and SCSQ score. A linear regression model was used to determine the influencing factors for anxiety or depression symptoms. RESULTS: The prevalence rates of anxiety and depression symptoms among doctors was 11.4% and 45.6%, respectively. History of depression or anxiety (T=-2.644, p= 0.010, 95%CI: -10.514~-1.481) was shown to be a risk factor for anxiety symptoms in doctors, while being male (T=2.970, p=0.004, 95%CI: 2.667~13.521) was a protective factor for depression. The prevalence rate of anxiety and depression symptoms among nurses was 27.9% and 43.0%, respectively. History of depression or anxiety was a common risk factor for anxiety symptoms (T=-3.635, p=0.000, 95%CI: -16.360~-4.789) and depression symptoms (T=-2.835, p=0.005, 95%CI:-18.238~-3.254) in nurses. The results of partial correlation analysis (controlled for gender and history of depression or anxiety) indicated that the total score of positive coping was negatively correlated with the total score of anxiety (r=-0.182, p=0.002) and depression (r=-0.253, p=0.001). CONCLUSIONS: The first-line anti-epidemic medical staff have high anxiety and depression symptoms and adopting positive coping styles will help to improve their negative emotions.

Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.

BACKGROUND: Colon cancer (CC) is a common malignant cancer. Recently, circFNDC3B was found to exert biological function in multiple cancers. However, it was unclear whether the potential protein encoded by circFNDC3B is involved in carcinogenesis of CC. METHODS: We used Sanger sequence and RNase R digestion assay to confirm the existence of circFNDC3B, and quantitative real-time PCR was used to evaluate the circRNA's expression. Then fluorescence in situ hybridization (FISH) was performed to study location of circFNDC3B. The identification of protein encoded by circFNDC3B was performed using LC-MS/MS. The function of circFNDC3B-218aa on proliferation, invasion and migration were assessed by CCK8 assays, colony formation assays, transwell assays, wound-healing assays and animal experiments. RNA-sequencing and western blot were used to identify the gene regulated by circFNDC3B-218aa. Finally, glucose metabolism-related assays were performed to further investigate function of circFNDC3B-218aa. RESULTS: CircFNDC3B was localized mostly in the cytoplasm, and was decreased in CC cell lines and tissues. The patients with low circFNDC3B expression had a shorter OS (P = 0.0014) than patients with high expression. Moreover, circFNDC3B inhibited the proliferation, invasion and migration of CC cells. Next, we identified that circFNDC3B could encode a novel protein circFNDC3B-218aa. Furthermore, circFNDC3B-218aa, not circFNDC3B, inhibited the proliferation, invasion and migration of CC. Additionally, the in vivo experiments implied that up-regulated circFNDC3B-218aa exhibited an inhibitory effect on CC progression. By RNA-sequencing, western blot and glucose metabolism-related assays, we found that circFNDC3B-218aa inhibited the expression of Snail, and subsequently promoted the tumor-suppressive effect of FBP1 in CC. CONCLUSIONS: The novel circFNDC3B-218aa may serve as a tumor suppressive factor and potential biomarker which may supply the potential therapeutic target for CC.

Nowadays, depression is the world’s major health concern and economic burden worldwide. However, due to the limitations of current methods for depression diagnosis, a pervasive and objective approach is essential. In the present study, a psychophysiological database, containing 213 (92 depressed patients and 121 normal controls) subjects, was constructed. The electroencephalogram (EEG) signals of all participants under resting state and sound stimulation were collected using a pervasive prefrontal‐lobe three‐electrode EEG system at Fp1, Fp2, and Fpz electrode sites. After denoising using the Finite Impulse Response filter combining the Kalman derivation formula, Discrete Wavelet Transformation, and an Adaptive Predictor Filter, a total of 270 linear and nonlinear features were extracted. Then, the minimal‐redundancy‐maximal‐relevance feature selection technique reduced the dimensionality of the feature space. Four classification methods (Support Vector Machine, K ‐Nearest Neighbor, Classification Trees, and Artificial Neural Network) distinguished the depressed participants from normal controls. The classifiers’ performances were evaluated using 10‐fold cross‐validation. The results showed that K ‐Nearest Neighbor (KNN) had the highest accuracy of 79.27%. The result also suggested that the absolute power of the theta wave might be a valid characteristic for discriminating depression. This study proves the feasibility of a pervasive three‐electrode EEG acquisition system for depression diagnosis.